Mechanical stretching of amyloid Abeta11-42 fibrils using steered molecular dynamics

TL;DR

This study uses steered molecular dynamics to investigate the mechanical properties of amyloid beta Abeta11-42 fibrils, revealing their rupture points and the high energy required for unfolding, which informs understanding of their stability.

Contribution

It provides detailed molecular insights into the rupture sites and energy barriers of amyloid beta fibrils under mechanical stress using SMD simulations.

Findings

Rupture occurs at alanine-glutamic acid interfaces.

Unfolding requires approximately 210 eV of free energy.

Fibrils are more stable in solution due to hydrophobic interactions.

Abstract

Mechanical strength of amyloid beta fibrils has been known to be correlated with neuronal cell death. Here, we resorted to steered molecular dynamics (SMD) simulations to mechanically stretch a single S-shape amyloid beta Abeta11-42 dodecamer fibril in vacuum. It was found that the weakest sites at which the fibril was ruptured due to mechanical extension were exclusively at the interfaces of alanine and glutamic acid distributed throughout the fibril. It was also revealed that the free energy required to unfold the fibril to form a long linear conformation is equivalent to ~ 210 eV, being several thousand times larger than thermal voltage at room temperature. As a consequence, within solution a larger free energy is needed for such a maximal stretching based on the fact that amyloid beta fibrils are structurally more stable in solution due to the interplay between their hydrophobic cores and solution's entropy.